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Abstract Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional gene silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. Additionally, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we found that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of a subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not linked to loss of Polycomb chromatin domains. Instead, PDS5A removal causes aberrant cohesin activity leading to ectopic insulation sites, which disrupt the formation of ultra-long Polycomb loops. We show that these loops are important for robust silencing at a subset of PRC1/PRC2 target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.

Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to promote gene silencing. Here the authors use reversible tethering of Polycomb proteins to ectopic sites in mouse ESCs and find that canonical but not variant PRC1 can trigger sequence-independent propagation of Polycomb-mediated transcriptional repression.

Vitiligo is a chronic depigmenting disorder that significantly impacts the quality of life of patients. Though there have been significant advancements in targeted therapies in skin diseases such as psoriasis or eczema, the progress in the treatment of vitiligo has been slow, with minimal studies assessing the effect of biologics, though there has been recent evidence of the effectiveness of JAK inhibition. This paper reviews the published case reports and studies for the use of systemic targeted therapies including biologics and JAK inhibitors in vitiligo., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Competing Interests: None disclosed.

Vitiligo is an autoimmune skin disorder resulting in the depigmentation of skin characterised by patches of varying sizes and shapes. A common disorder of pigmentation that affects 0.5%-2% of the global population. Despite its well-understood autoimmune pathogenesis, the targets for effective cytokine intervention remain unclear. Current first-line treatments include oral or topical corticosteroids, calcineurin inhibitors and phototherapy. These treatments are limited, have varying efficacies, and are associated with significant adverse events or can be time-consuming. Therefore, biologics should be explored as a potential treatment for vitiligo. There are currently limited data for the use of JAK and IL-23 inhibitors for vitiligo. A total of 25 studies were identified in the review. There is promising evidence regarding the use of JAK and IL-23 inhibitors for the treatment of vitiligo., (© 2023 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Dupilumab is a first-in-class biologic approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of multiple atopic diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Since gaining traction as an effective treatment modality, multiple reports have highlighted the many ocular side effects associated with dupilumab usage. These range from mild diseases, such as conjunctivitis, dry eyes, and blepharitis, to more severe manifestations such as intraocular inflammation and cicatrizing conjunctivitis. The pathogenesis behind these manifestations remains controversial, but are likely multi-factorial. We review the current evidence surrounding ocular manifestations of dupilumab-associated disease and proposed treatments to provide an overview of this unique disease entity. With increasing usage of dupilumab, formal recommendations regarding the treatment of dupilumab-associated ocular disease are warranted to provide standardized clinical guidance. Furthermore, it is important for health care practitioners to remain abreast with existing literature to counsel and empower patients with the knowledge surrounding contemporary treatments for atopic diseases and their associated sideeffects., (Copyright © 2022. Published by Elsevier Inc.)

Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow-band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy., (© 2021 Wiley Periodicals LLC.)

Background: The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared., Objective: To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools., Methods: An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures., Results: The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other., Conclusion: Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities., Competing Interests: Dr Dedee F. Murrell developed the EBDASI. Dr Dedee F. Murrell and Authors Daniel and Su were involved in the validation of the EBDASI. Dr Kern and authors Rogers, Gibson, Martin, Robertson, Feng, and Oliver G. C. Murrell have no conflicts of interest to declare., (© 2020 Published by Elsevier on behalf of the American Academy of Dermatology, Inc.)

Background: Psoriasis is a common immune-mediated skin condition that affects at least 2% of the Australian population. Though psoriasis was often considered a cutaneous condition alone, more recent literature has shown other organ involvement. These comorbidities may be missed unless specifically looked for., Objective: The aim of this article is to outline the well-recognised comorbidities associated with psoriasis to facilitate a discussion for general practitioners (GPs) to have with their patients about lifestyle changes, the need to screen for other diseases and management of comorbidities., Discussion: GPs are in a prime position to screen, diagnose and manage comorbidities in a patient with psoriasis. GPs have a broad understanding of and exposure to general medicine and are in a privileged position of seeing many patients with psoriasis within the spectrum of the disease.

Autoimmune Blistering Diseases of the Pemphigoid type is characterised by sub-epidermal blisters (SEB) with circulating autoantibodies against components of the basement membrane zone (BMZ). The main disorders to date include bullous pemphigoid (BP), pemphigoid gestationis, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), linear IgA disease (LABD), dermatitis herpetiformis (DH), lichen planus pemphigoides and bullous lupus. This is in contrast to pemphigus and related disorders, which demonstrate intraepidermal acantholysis and a positive Nikolsky sign. The classification and management is based on clinical, histological and direct and indirect immunofluorescence findings. There are, however, overlapping clinical and histological features between the conditions and clinical heterogeneity within each disease., (© 2019 European Academy of Dermatology and Venereology.)

Knowledge with regard to the pathogenesis of lupus erythematosus has progressed rapidly over the past decade, and with it has come promising new agents for the treatment of cutaneous lupus erythematous (CLE). Classification of CLE is performed using clinical features and histopathologic findings, and is crucial for determining prognosis and choosing therapeutic options. Preventative therapy is critical in achieving optimal disease control, and patients should be counseled on sun-safe behavior and smoking cessation. First-line therapy includes topical corticosteroids and calcineurin inhibitors, with antimalarial therapy. Traditionally, refractory disease was treated with oral retinoids, dapsone, and other oral immunosuppressive drugs, but new therapies are emerging with improved side effect profiles and efficacy. Biologic agents, such as belimumab and ustekinumab, have been promising in case studies but will require larger trials to establish their role in routine therapy. Other novel therapies that have been trialed successfully include spleen tyrosine kinase inhibitors and fumaric acid esters. Finally, new evidence has been published recently that describes safer dosing regimens in thalidomide and lenalidomide, both effective medications for CLE. Given the chronic disease course of CLE, long-term treatment-related side effects must be minimized, and the introduction of new steroid-sparing agents is encouraging in this regard., (© 2019 Published by Elsevier Inc. on behalf of Women's Dermatologic Society.)

Background/objectives: This study documents the perspectives of Australian dermatologists on the adequacy of teaching and training in skin of colour (SOC), and their confidence in diagnosing and treating common medical, surgical and cosmetic issues in SOC and to gauge their desire for further training in this area., Methods: Surveys were distributed to Australasian Dermatologists during their annual scientific meeting in Melbourne, Australia in 2014. Completed surveys from dermatologists nationwide were collected and evaluated. Altogether 270 surveys were distributed., Results: In total, 140 surveys were completed and returned. Four surveys were excluded as they were completed by dermatologists who were not practicing in Australia. Thus, 136 surveys were deemed appropriate for analysis. While 75% of participants were confident in managing common medical issues in SOC 85% were not confident in managing common cosmetic issues in SOC and 75% were not confident performing procedures on SOC. Over 80% stated they would have liked more teaching in SOC during their training and over 50% of those surveyed believe they had enough time to undertake further training in this area., Conclusion: We propose here the first analysis of issues relating to SOC dermatology among Australian dermatologists in the context of the changing patient demographic in the country. The findings of this survey clearly demonstrate there is a need and desire for more training in medical, cosmetic and procedural aspects of SOC dermatology and that most of the Australian dermatologists surveyed have the desire and time to undertake such training., (© 2016 The Australasian College of Dermatologists.)

Background: Atopic dermatitis (AD) assessment is more difficult in patients with skin of colour (SOC)., Objectives: To compare the reliability of commonly used outcome measures for assessing AD in patients with SOC and to evaluate a novel greyscale in this population., Methods: Twenty-five patients with AD each attended a 1-day scoring exercise based in either Sydney or Melbourne, Australia. Each patient was scored by the same five physicians using the Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator's Global Assessment (IGA) and a novel greyscale. Patients also completed the Patient-Oriented Eczema Measure and quality-of-life measures. A Mexameter was used to measure baseline melanin indices. Ten random patients were rescored to test intrarater reliability., Results: We included 11 light-skinned patients (melanin index ≤ 200) and 14 patients with SOC (melanin index > 200) in the cohort. The inter-rater intraclass correlation coefficients (ICCs) were EASI 0·83 [95% confidence interval (CI) 0·66-0·94] for light skin and 0·77 (95% CI 0·60-0·91) for SOC; oSCORAD 0·68 (95% CI 0·44-0·88) for light skin and 0·74 (95% CI 0·54-0·89) for SOC; and IGA 0·80 (95% CI 0·62-0·93) for light skin and 0·70 (95% CI 0·49-0·87) for SOC. The greyscale had an ICC of 0·78 (95% CI 0·60-0·91) when replacing the EASI's erythema scale for patients with SOC. All scores showed excellent intrarater reliability for all skin types. Erythema component analysis showed that erythema did not contribute to variability., Conclusions: EASI showed excellent reliability for patients of all skin colours, and is recommended as the optimal core measure for patients with all skin colours., (© 2016 British Association of Dermatologists.)

Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children., (© 2015 The Australasian College of Dermatologists.)

Background: There are multiple severity outcome measures for atopic dermatitis (AD). There is a need to compare the reliability of these measures., Objectives: To compare the inter-rater and intrarater reliability of the objective Scoring Atopic Dermatitis (oSCORAD), Eczema Area and Severity Index (EASI), Six Area, Six Sign Atopic Dermatitis (SASSAD) and Three Item Severity index (TIS); and to analyse the correlation between these outcome measures and the quality-of-life instruments Patient-Orientated Eczema Measurement, Dermatology Life Quality Index and Skindex-29., Methods: Twelve patients with AD attended a 1-day scoring exercise by five trained dermatology clinicians. Inter-rater and intrarater reliability were assessed using the intraclass correlation coefficient (ICC). Correlation between clinician-rated and patient-reported measures was analysed using Spearman's rho., Results: Regarding inter-rater reliability, EASI and SASSAD showed good reliabilities, with ICCs of 0·730 [95% confidence interval (CI) 0·500-0·900] and 0·680 (95% CI 0·440-0·880), respectively. However, the ICCs were poor for TIS and oSCORAD, with 0·497 (95% CI 0·233-0·785) and 0·498 (95% CI 0·234-0·785), respectively. Separate body surface area (BSA) component analyses showed that the oSCORAD BSA component contributed to its inter-rater variations. Regarding intrarater reliability, EASI and TIS showed excellent ICCs of 0·886 (95% CI 0·744-0·952) and 0·820 (0·614-0·923), respectively, while SASSAD showed a good reliability with an ICC of 0·720 (95% CI 0·424-0·878). However, the intrarater ICC was poor for oSCORAD, with 0·446 (95% CI 0·037-0·730). Regarding correlation with patient-reported measures, only SASSAD demonstrated moderate correlation with Skindex-29 (ρ = 0·611, P = 0·035)., Conclusions: EASI demonstrated the highest inter-rater and intrarater reliability, supporting it as the optimal AD severity outcome measure., (© 2015 British Association of Dermatologists.)

Topical corticosteroids are used frequently in dermatology and atopic dermatitis without significant adverse effects. Though ocular diseases such as glaucoma and cataracts are known complications of systemic corticosteroids, the role of topical corticosteroids is limited to case reports. This review assesses the literature regarding topical steroids and their role in ocular diseases. There is evidence of harm to vision when potent topical corticosteroids are inappropriately used for prolonged periods to periorbital sites. There is no evidence to date that weak TCS to the face or potent TCS to areas other than the eyes results in ocular complications. Further research trials are required in this area., (© 2015 The Australasian College of Dermatologists.)

Vitiligo is a common depigmenting disease that can affect the skin and mucosal surfaces. Various treatments have been used over the years with varying repigmentation rates. This review looks at the evidence of commonly used therapies for vitiligo., (© 2014 The Australasian College of Dermatologists.)

Background: Anemia is a common complication of epidermolysis bullosa (EB). To date, no extensive data on the prevalence of anemia in EB patients have been well characterized worldwide., Objective: To determine and to characterize the prevalence of anemia in the Australian EB population by conducting a retrospective cross-sectional study., Methods: All ( n = 368) EB patients registered in the Australasian Epidermolysis Bullosa Registry (AEBR) from 2006 to 2012 were reviewed for pathological evidence of anemia. Patients with EB without anemia and those without hematological parameters were excluded from the study. Patients' particulars were separated into pediatric (< 18 years old) and adult (≥ 18 years old) male and female subgroups., Results: One-hundred sixty-nine out of 368 EB patients had eligible blood results to be analyzed, as milder forms of EB did not routinely have laboratory testing; 27.8% ( n = 47/169) of EB patients were anemic at any time point in their lifetime. All generalized severe junctional EB (JEB-GS) cases (100%, n = 4/4); 68.0% ( n = 17/25) of recessive dystrophic EB (RDEB); and 37.5% (n = 6/16) of generalized intermediate JEB (JEB-I) patients were anemic., Limitations: As EB is an orphan disease, the limited sample size may have affected the significance of the study result., Conclusion: The high prevalence of anemia seen in RDEB and JEB generalized severe (JEB-GS) patients in our cohort is similar to those reported in case series.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pemphigus is an autoimmune blistering disease characterized by cutaneous and mucosal blisters and erosions. Though systemic corticosteroids have been the mainstay of treatment for pemphigus over the years, more recently research has focused on steroid-sparing agents. This review looks at the commonly used steroid-sparing agents in pemphigus and the evidence from randomized controlled trials (RCTs) supporting their use.

Background: There is a lack of validated standardized outcome measures for epidermolysis bullosa (EB) that can separate activity from damage., Objective: We sought to develop and validate an instrument for inherited EB of all ages and subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores activity responsive to therapy separately from scarring., Methods: The EBDASI was validated by comparing its reliability and validity against the Birmingham EB Severity (BEBS) score (partially validated with activity mixed with scarring), using the Physician Global Assessment (PGA) scale as a reference measurement. Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2 junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad hoc basis during routine patient clinic were also included., Results: For interrater reliability, the overall total score intraclass correlation coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS 0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926 (0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation with PGA (ρ = 0.871) than BEBS with PGA (ρ = 0.852). Intraclass correlation coefficients scatterplots showed the EBDASI was better at distinguishing milder forms of EB, with better correlations at higher severity scores than the BEBS., Limitations: A limited number of patients were recruited for this study. An independent study will be required to demonstrate the responsiveness of the EBDASI., Conclusion: The EBDASI demonstrated excellent reliability and validity, as compared with 2 other outcome measures., (Copyright © 2013 American Academy of Dermatology, Inc. All rights reserved.)

Background: Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment., Objectives: To develop a quality of life instrument specific to the effects of treatments used in patients with autoimmune bullous disease (AIBD)., Methods: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL, selecting only those questions pertaining to the treatment effects. This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire was administered to 70 patients, before factor analysis was performed to yield the final questionnaire of 17 questions. Validity and reliability were evaluated across a range of indices., Results: Face and content validity were established through a comprehensive patient interview process, expert review and summaries of treatments used. The questionnaire was found to have appropriate correlation with the Dermatology Life Quality Index (r = 0.64) and the level of treatments used (P < 0.01), and was found to be responsive to overall variations in treatment burden. The TABQOL was also found to be a reliable instrument as evaluated by internal consistency (Cronbach α = 0.892) and test-retest reliability (r = 0.99)., Conclusions: We have shown that the TABQOL questionnaire is a valid and reliable instrument that may to be used to measure treatment burden in AIBD and serve as an end point in clinical trials., (© 2013 British Association of Dermatologists.)